Abnormal P-wave terminal force in lead V₁ is a marker for atrial electrical dysfunction but not structural...

There is a lack of diagnostic and therapeutic options for patients with atrial cardiomyopathy and paroxysmal atrial fibrillation. Interestingly, an abnormal P-wave terminal force in electrocardiogram lead V₁ (PTFV₁ ) has been associated with atrial cardiomyopathy, but this association is poorly understood. We investigated PTFV₁ as a marker for functional, electrical, and structural atrial remodelling.

Fifty-six patients with acute myocardial infarction and 13 kidney donors as control cohort prospectively underwent cardiac magnetic resonance imaging to evaluate the association between PTFV₁ and functional remodelling (atrial strain). To further investigate underlying pathomechanisms, right atrial appendage biopsies were collected from 32 patients undergoing elective coronary artery bypass grafting. PTFV₁ was assessed as the product of negative P-wave amplitude and duration in lead V₁ and defined as abnormal if ≥4000 ms*μV. Activity of cardiac Ca/calmodulin-dependent protein kinase II (CaMKII) was determined by a specific HDAC4 pull-down assay as a surrogate for electrical remodelling. Atrial fibrosis was quantified using Masson's trichrome staining as a measure for structural remodelling. Multivariate regression analyses were performed to account for potential confounders. A total of 16/56 (29%) of patients with acute myocardial infarction, 3/13 (23%) of kidney donors, and 15/32 (47%) of patients undergoing coronary artery bypass grafting showed an abnormal PTFV₁ . In patients with acute myocardial infarction, left atrial (LA) strain was significantly reduced in the subgroup with an abnormal PTFV₁ (LA reservoir strain: 32.28 ± 12.86% vs. 22.75 ± 13.94%, P = 0.018; LA conduit strain: 18.87 ± 10.34% vs. 10.17 ± 8.26%, P = 0.004). Abnormal PTFV₁ showed a negative correlation with LA conduit strain independent from clinical covariates (coefficient B: -7.336, 95% confidence interval -13.577 to -1.095, P = 0.022). CaMKII activity was significantly increased from (normalized to CaMKII expression) 0.87 ± 0.17 to 1.46 ± 0.15 in patients with an abnormal PTFV₁ (P = 0.047). This increase in patients with an abnormal PTFV₁ was independent from clinical covariates (coefficient B: 0.542, 95% confidence interval 0.057 to 1.027, P = 0.031). Atrial fibrosis was significantly lower with 12.32 ± 1.63% in patients with an abnormal PTFV₁ (vs. 20.50 ± 2.09%, P = 0.006), suggesting PTFV₁ to be a marker for electrical but not structural remodelling.

Abnormal PTFV₁ is an independent predictor for impaired atrial function and for electrical but not for structural remodelling. PTFV₁ may be a promising tool to evaluate patients for atrial cardiomyopathy and for risk of atrial fibrillation.